Study Suggests Extranodal Extension Should be Included in Lymph Node Classification of Cutaneous HNSCC


Investigators found that the number of metastatic lymph nodes and the presence of extranodal extension are complementary for predicting disease-specific survival in head and neck squamous cell carcinoma, suggesting the necessity of incorporating these factors into staging systems.

A retrospective analysis published in Cancer indicated that the number of metastatic lymph nodes and the presence of extranodal extension (ENE) in cutaneous head and neck squamous cell carcinoma (HNSCC) are independent prognostic factors for disease-specific survival (DSS).

Additionally, the study investigators suggested that the incorporation of these factors into staging systems may improve the performance of the American Joint Committee on Cancer (AJCC) lymph node classification.

“The proposed system should be considered in future reviews of the AJCC TNM classification system after external validation,” wrote the study authors, led by Moran Amit, MD, PhD.

In this study, a total of 1258 patients with cutaneous HNSCC who had undergone surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center were included. Investigators then evaluated the prognostic performance of the AJCC lymph node classification system compared with a modified model which incorporated ENE with the number of metastatic lymph nodes.

The primary end point was DSS and key secondary end points included local, regional, and distant metastases-free survival. To assess the fitness of each staging model, recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were utilized.

Overall, no significant differences were observed in 5-year DSS rates between patients with pathologic lymph node–negative (pN0) disease and those with pN-positive/ENE-negative disease (67.4% vs 68.2%; HR, 1.02; 95% CI, 0.61-1.79) or between those with pN-positive status and either ENE-negative or -positive disease (68.2% vs 52.7%; HR, 0.57; 95% CI, 0.31-1.01).

However, when comparing risk, the RPA-derived model achieved better stratification between high- (category III, ENE-positive with >2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with >2 positive lymph nodes). Moreover, the performance of the RPA-derived model was also better than that observed with the pathologic TNM classification (Akaike information criterion score, 1167 versus 1176; Bayesian information criterion score, 1175 versus 1195).

“In the current study, we observed that these features, ie, the number of metastatic lymph nodes and the presence of ENE, are complementary,” the authors explained. “Hence, a staging system that incorporates both features, such as the RPA-derived model proposed here, will perform better than the existing lymph node classification system. The role of ENE as a prognostic feature is particularly important in cutaneous SCC because the rates of lymph node metastasis are lower than in mucosal SCC, and both therapeutic and elective neck dissections are performed less commonly in cutaneous SCC.”

Importantly, though the current results represent a single-center cohort of patients, a potential limitation is the risk of inconsistent surgical technique and processing of the pathologic specimens. However, the yield of neck dissection in this cohort of patients was found to be similar to previously reported mean lymph node yields, with similar variations in the total number of excised lymph nodes observed.


Amit M, Liu C, Gleber-Netto FO, et al. Inclusion of extranodal extension in the lymph node classification of cutaneous squamous cell carcinoma of the head and neck. Cancer. Published online December 15, 2020. doi:10.1002/cncr.33373

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